Hyperhomocyst(e)inemia and Risk of Ischemic Stroke Among Young Asian Adults

Background and Purpose— Hyperhomocyst(e)inemia is emerging as a possible risk factor for stroke, possibly because of accelerated atherosclerosis. There are no previous publications evaluating homocyst(e)ine in young Asian ischemic stroke patients. We conducted a case-control study examining homocyst(e)ine, vitamin B12, and folate levels in young, first-ever Asian ischemic stroke patients. Methods— We prospectively recruited 109 consecutive young (<50 years) first-ever hospitalized ischemic stroke patients and 88 age/gender-matched hospital-based controls during a period of 18 months. Prevalence of vascular risk factors was assessed; fasting homocyst(e)ine, vitamin B12, and folate were assayed. Stroke mechanisms were subtyped using TOAST study criteria. Results— Mean age was 43.8 (cases) and 43.1 (controls) years; 71.6% were male (cases and controls). Diabetes mellitus, hypertension, and hyperlipidemia were significantly more prevalent in cases. Mean fasting homocyst(e)ine levels were significantly higher in cases (13.7 &mgr;mol/L, 95% CI: 12.7 to 14.9) than controls (10.8 &mgr;mol/L, 95% CI: 9.9 to 11.8, P <0.001). Mean vitamin B12 levels were significantly lower in cases (299.5 pmol/L, 95% CI: 266.7 to 332.3) than controls (394.5 pmol/L, 95% CI: 357.9 to 431.0, P <0.001). Folate levels were not significantly different. Mean homocyst(e)ine levels were significantly elevated in large-artery strokes (16.9 &mgr;mol/L, 95% CI: 14.5 to 19.7, P <0.001) but not other stroke subtypes compared with controls. Compared with the lowest homocyst(e)ine quartile, the highest quartile was significantly associated with an adjusted odds ratio of 4.3 for ischemic stroke and 25.3 for large-artery stroke. Using a logistic regression model, the adjusted odds ratio was 5.17 (95% CI: 1.96 to 13.63, P =0.001) for every 1 &mgr;mol/L increase in log homocyst(e)ine. Conclusions— Hyperhomocyst(e)inemia is an independent risk factor for ischemic strokes in young Asian adults. The relationship between increasing homocyst(e)ine and stroke risk is strong, graded, and significant. The association with large-artery strokes suggests that hyperhomocyst(e)inemia may increase stroke risk via a proatherogenic effect.